The ideal sedative agent for use in ICU probably does not exist. All sedative agents cause some degree of cardiovascular instability in critically ill patients. Longer-acting agents can be given by bolus, but may accumulate and do not allow rapid change in response to alterations in a patient’s condition. Shorter-acting agents are often preferred because they can be given by infusion, are less likely to accumulate and allow rapid change in depth, but they can be difficult to titrate.

In general single agents are not effective, either because they fail to achieve all the goals of sedation or because of unacceptable side-effects as the dose is increased. For this reason, it is more common to use a tailored combination of drugs. The principle employed is similar to that of ‘balanced anaesthesia’. By combining the benefits of more than one class of agent, satisfactory levels of sedation can be achieved at much lower doses than could be achieved using either agent alone, thus allowing some of the adverse effects of individual agents to be reduced. A typical combination is that of an opioid (e.g. fentanyl) together with a benzodiazepine (e.g. midazolam). This combination provides analgesia, sedation and anxiolysis. The advantages and disadvantages of these agents are shown in Table 3.1.

TABLE 3.1 Advantages and disadvantages of opioids and benzodiazepines for ICU sedation

The choice of agents will depend on local protocols and the clinical condition of the patient. If the balance of a patient’s problem is pain, then analgesia is the main requirement. Epidural anaesthesia, other regional anaesthetic techniques and patient-controlled analgesia (PCA) may be useful. (See Postoperative analgesia, p. 349.) If the balance of the patient’s problem is agitation, then the main requirement may be for sedative or anxiolytic agents. Haloperidol and other major tranquillizers are appropriate for the treatment of delirium and psychosis and recent guidelines have placed greater emphasis on the use of these agents (see Acute confusional states below). Tables 3.2 and 3.3 provide a guide to commonly used analgesic and sedative drugs.

TABLE 3.2 Commonly used analgesic agents

TABLE 3.3 Commonly used sedative agents (doses based on 70 kg adult)

Propofol is perhaps one of the most widely used sedative agents in adult ICU. Bolus doses of 1–3 mg / kg are sufficient to induce anaesthesia (e.g. prior to intubation). Smaller doses of 10–20 mg repeated to effect may be useful for increasing the depth of sedation, e.g. prior to suction or painful procedures.

There have been ongoing reports of inhaled anaesthetic agents being used for sedation in critical care. These may be of value in specific circumstances. Isoflurane and other volatile agents may be useful in asthma and severe bronchospasm because of their bronchodilator properties. Specific systems for delivering volatile agents into ventilator circuits on the ICU have been developed. Nitrous oxide may be of value for changes of burns dressings, but should not be used for more than 12 h because of bone marrow suppression.

Ideally patients should be awake, pain-free, able to move about as much as possible and be able to cooperate with physiotherapy and nursing care. Excessive sedation should be avoided. The potential problems associated with over-sedation include:

prolonged need for IPPV / intubation

haemodynamic instability

gastrointestinal tract stasis

potential immune suppression

potential organ toxicity

difficulty in assessing neurological state

increased withdrawal phenomena, delirium, hallucinations and nightmares in the post-critical illness period.

To avoid excessive sedation, agents should be titrated according to the balance of the patient’s needs. In practice, this can be difficult. The requirement for sedation differs markedly between patients. Younger, fitter patients generally require more sedative and analgesic drugs. Patients who abuse alcohol and other centrally acting drugs may be very difficult to sedate because of cross-tolerance between the abused substance and the prescribed sedative or analgesic agents. Relatives and patients may deny or conceal such abuse. Acute tolerance to drugs used for sedation in ICU may also occur.

In addition, the pharmacokinetics of many sedative drugs used in critical illness is poorly understood. Only limited information is available on drug metabolism and excretion in the critically ill. Drug trials performed in rats, healthy ‘volunteers’, ASA I patients and patients with compensated cirrhosis and uraemia are of little relevance to the critically ill ICU patient, in whom abnormalities in the distribution, metabolism and elimination of drugs are common. Regular reassessment of the need for, and level of, sedation is therefore required.

Sedation scoring systems may be useful in helping titrate levels of sedation. A typical score (performed hourly) together with appropriate responses is shown in Table 3.4.

TABLE 3.4 Sedation score

Where drugs are given by continuous infusion accumulation can occur and studies have consistently shown that patients tend to be over-sedated. Regular reassessment of sedation, and the use of sedation-free periods or ‘sedation holds’ can reduce the duration of tracheal intubation and ventilatory support. Many units now consider sedation holds on a daily basis. Typically sedation (not analgesia) is stopped once a day, to allow assessment. Ideally, sedation is held until the patient is able to follow commands.

Check that sedative infusions are running correctly and at the prescribed dose.

Exclude possible causes of agitation, including: full bladder, painful wounds, hypoxia, hypercarbia, and endotracheal tube touching carina.

Review other drug therapy and stop where appropriate. Many drugs (for example H₂ blockers) have the potential to induce confusional states.

Consider tracheostomy or nasal intubation. These are often better tolerated, and allow sedative and analgesic drugs to be significantly reduced.

Consider alternative sedative / analgesic agents if appropriate (e.g. paracetamol, NSAIDs, gabapentin, tricyclics). Seek advice.

Consider alternative analgesic techniques if appropriate (e.g. epidural or regional nerve blocks).

Eventually all patients need to be weaned off sedative agents. There is often a difficult phase during which the patient is partially sedated but unable to cooperate due to residual drug effects. Real problem patients (e.g. after head injury or suffering from withdrawal of drugs or alcohol), may be best nursed on a mattress on the floor. This reduces risk of harm should the patient fall out of bed. (See Withdrawal phenomena / acute confusional states below.)

If a patient fails to regain full consciousness after sedative and analgesic drugs have been stopped for a period of time, the question invariably arises as to ‘why?’ This may be due to the accumulation of drugs or their active metabolites, which resolves with time, but other causes of coma or ‘apparent coma’ should be excluded. Consider:

Effects of sepsis. Encephalopathy is common (for example as part of multiple organ failure).

Metabolic derangement / encephalopathy.

Seizure activity.

Structural brain damage (including CVA, hypoxic brain injury).

Awake patients who cannot respond (‘locked-in syndrome’).

Residual neuromuscular blockade (see p. 45).

Critical illness neuromyopathy (see p. 304).

Severe muscle weakness is common following critical illness so it may not be immediately apparent that the patient is actually awake, but unable to move. A similar clinical picture may also be seen in the presence of pontine lesions (e.g. following central pontine myelinolysis or brainstem stroke). Careful clinical examination is required to ascertain the true clinical picture. An EEG and CT scan may be helpful. If no other cause of coma can be established and failure to wake up is considered to result from the accumulation of sedative agents, a trial of naloxone or flumazenil may occasionally be diagnostic (Table 3.5). This is not without risk, however, and may precipitate convulsions. Seek senior advice.

TABLE 3.5 Naloxone and flumazenil

* Both drugs have a short half-life (approximately 20 min), leading to the risk of recurrence of respiratory depression and sedation. Side-effects include fits, hypertension, and dysrhythmias. Do not infuse over long periods of time. Ventilate the patient and await resolution as redistribution and metabolism of drugs occur!

When drugs used before admission, or sedative drugs given in ICU are stopped, drug withdrawal states may develop. This may result in seizures, hallucinations, delirium tremens, confusional states, agitation and aggression. Elderly patients are particularly susceptible. These phenomena are difficult to control without further heavy sedation, but usually settle over time. You should look for and treat any reversible causes of confusion (Box 3.1).

Drugs that can be useful for the control of acute confusional states, including those induced by the withdrawal of mixed sedative agents, are shown in Table 3.6. You should generally seek senior advice before resorting to these agents.

TABLE 3.6 Drugs for the treatment of acute confusional states

* Large number of actions and side-effects. Particularly beware of alpha blockade and hypotension. (Numerous newer antipsychotic agents, e.g. olanzapine, are now available. Seek advice.)

Only used by bolus injection for endotracheal intubation, 1 mg / kg i.v. bolus.

This is a short-acting depolarizing muscle relaxant, which gives good intubating conditions in less than a minute. It is useful for rapidly intubating patients in an emergency and has the advantage for the inexperienced that it has a short duration of action (2–4 min), so that if intubation is difficult, spontaneous respiratory effort is rapidly re-established. In a small number of patients, however, the effects are prolonged because of a genetic abnormality in the cholinesterase enzyme, which breaks down suxamethonium.

Side-effects associated with the use of suxamethonium include bradycardia, hypotension, and increased salivation and bronchial secretions. These can be blocked by the use of atropine. Intraocular pressure and intracranial pressure are transiently increased. All patients suffer a small increase (0.5–1 mmol / L) in serum potassium following suxamethonium. The drug should therefore be avoided in patients with hyperkalaemia. In some groups of patients, this increase in potassium may be much greater and may result in a cardiac arrest. It is also best avoided in all patients with pre-existing neuromuscular disease. Contraindications to the use of suxamethonium are shown in Box 3.2.

If it is necessary to use a muscle relaxant for intubation, as an alternative to suxamethonium, non-depolarizing muscle relaxants (see below) can be used as part of a ‘modified rapid sequence induction’. Any non-depolarizing muscle relaxant could theoretically be used at relatively high dose for this purpose. Rocuronium, however, has the fastest onset of action. Moreover, a specific antagonist to rocuronium is now available, so the effects may be rapidly reversed if intubation proves difficult. (See Practical procedures, p. 398.)

The use of muscle relaxants should be regularly reviewed and consideration given to stopping them intermittently to assess the adequacy of sedation. Neuromuscular blockade can be monitored if required using nerve stimulators. On the ICU this is most commonly required to exclude residual muscle paralysis, for example prior to performing brainstem death tests. An electric current is passed through a peripheral nerve and the response of the muscle supplied by that nerve observed. A common method of assessment is to produce four impulses, 0.5 s apart, known as a train of four (TO4), followed by a period of continuous tetanic stimulation at 50 Hz and then another train of four. Typical responses are shown in Figure 3.1.

Fig. 3.1 Monitoring neuromuscular function – typical patterns. TO4 represents ‘train of four’ stimulation, 50 Hz represents maximal tetanic stimulation.

Other than for intubation purposes, it is usually unnecessary to completely abolish all muscle response. When using non-depolarizing muscle relaxants by infusion, 75–90% block is usually adequate. This equates to one or two twitches present on a train of four.

In the majority of cases in ICU the effects of muscle relaxant drugs are allowed to wear off over time. Occasionally it may be appropriate to reverse the action of non-depolarizing drugs. This can usually be achieved with anticholinesterase drugs once there is some evidence of recovery of muscle function as demonstrated by the presence of two or three twitches on TO4.

A new drug, sugammadex, has recently become available that selectively binds and inactivates rocuronium and vecuronium, but not other non-steroid structure muscle relaxant drugs. This can rapidly reverse the effects of rocuronium (and to a lesser extent vecuronium and possibly pancuronium) even when only just administered.

The ICU is a very noisy place and often the only lighting is artificial. Patients may spend long periods in the same room with little knowledge of the outside world. The appreciation of day and night may be lost, resulting in disturbed sleep patterns. In addition, sedative drugs abolish rapid eye movement (dream) sleep and this can cause marked psychological disturbance, particularly during the convalescent stage.

Communication difficulties following tracheal intubation have not been adequately resolved. Written messages and letter boards are cumbersome, and lip reading is often difficult. Speaking aids for ventilated patients are available in the form of an artificial larynx to produce tones, but none is satisfactory for acute use as they take time and practice to work well. Speaking tracheostomy tubes or tracheostomy tube cuff deflation may be helpful in the recovery phase of illness.

Patients in intensive care are totally dependent both on the nursing staff for their personal needs, and on machines and drugs. In addition, they may be repeatedly visited by large groups of doctors and other staff. This may be humiliating and depersonalizing.

Many patients in intensive care will have painful surgical wounds and many will also have stiff painful limbs and joints as a result of immobility and critical illness neuropathy (see p. 304). Almost all will be subjected to repeated, potentially painful, procedures. Patients may be aware how sick they are, or even that they are dying. The overall experience is very frightening.

To reduce the impact of these problems, think about the psychological care of your patients. In particular:

Take time to get to know patients. Acknowledge their fears and anxieties. Give appropriate explanations and reassurance.

Respect patient privacy as much as possible.

Avoid unnecessarily large ward rounds and talking over the patient.

Always explain procedures to patients and provide adequate analgesia or anaesthesia.

Avoid disturbing the patient at night if possible. Encourage daytime stimulation in the form of visits from relatives and children, television and radio, all of which improve morale.

Despite every effort, many patients on ICU will suffer distressing, vivid nightmares and dreams during their stay. Some will develop apparent psychoses, which require treatment. Others (particularly long-stay patients) may become markedly depressed and withdrawn. Consideration should be given to the use of antidepressant therapy, although there are arguments against its use in ‘reactive’ depression. Amitriptyline (or similar agent) at night may aid nocturnal sleep and help to elevate mood and motivation, but may be associated with excessive sedation, lasting well into the following day. Fluoxetine given in the morning is an alternative. Advice may be sought from local ‘liaison psychiatry’ services.

One of the roles of the intensive care follow-up clinic is to facilitate better recognition and earlier, more appropriate management of the late psychological sequelae of intensive care, including post-traumatic stress disorder. (See ICU follow-up clinics, p. 15.)

At cellular level: hypoxia, acidosis, toxins and the effects of drugs can interfere with ionic pump mechanisms and lead to alterations in normal electrolyte balances and requirements.

Fluid shifts and increased losses can be associated with altered electrolyte balance.

Altered gastrointestinal and renal function further impair electrolyte homeostasis.

In addition, the underlying condition, repeated venesection and multiple procedures may lead to the need for repeated blood transfusions. Significant coagulopathy may require use of other blood products such as fresh frozen plasma (FFP) and platelet concentrates. There is frequently a requirement for multiple drug infusions. All these factors and additional volumes of fluid need to be taken into account when managing fluid and electrolyte balance.

The aim is to keep the patient hydrated, with an adequate circulating volume and normal electrolytes. Exact fluid regimens will depend on the patient’s clinical state of hydration (look at tongue, mucous membranes, tissue turgor, urine output), cumulative fluid balance on the daily charts, and electrolyte investigations.

Measure 24-h fluid balance accurately. The nurses will usually record the totals of all fluids, in and out, hourly. This will include all intravenous and nasogastric fluids, all drugs and all measurable losses. (It does not include unmeasurable insensible losses or shifts between intra- and extravascular spaces.)

Measure serum electrolytes frequently. Sodium (Na⁺) and potassium (K⁺) at least every 4–6 h in sicker patients. Magnesium (Mg²⁺), calcium (Ca²⁺) and phosphate (PO₄³⁻) daily or as required. Increasing Na⁺ and urea suggest dehydration.

Additional measurements such as plasma and urinary osmolality and urinary electrolytes are useful in difficult cases. (See Oliguria, p. 188.)

A typical fluid regimen for a 70 kg adult patient not receiving nutritional support, and with normal renal function, is shown in Table 3.10.

TABLE 3.10 Typical fluid management in 70 kg adult with normal renal function

Despite careful fluid management patients frequently become significantly fluid-overloaded, as measured by positive fluid balance and generalized oedema. This usually reflects the severity of the underlying clinical condition and resolves as the patient’s condition improves.

Measurement of patients’ weight as a means to aiding fluid management has never proved to be that useful due to difficulties in accurate measurement. In addition, progressive loss of lean body mass and fat in the immobilized critically ill patient over time make baseline measurements unrepresentative of ideal weight.

Review the fluid balance and regimen regularly and adjust it as necessary. If in doubt, consider a fluid challenge or a trial of diuretics. A low dose of a diuretic [for example 10–20 mg furosemide (frusemide)] often produces a good diuresis in the overloaded patient, with little effect in others. This effect has been attributed to the ‘overcoming’ of SIADH. (See Oliguria, p. 188.)

Disturbances of fluid and electrolyte balance are discussed further in Chapter 8.

Many of the intravenous fluids used in critical care are not ‘balanced salt solutions’, i.e. their ionic composition does not mirror that of physiological fluids. Commonly, both crystalloid and colloid solutions are based on ‘normal’ saline, which has a chloride content equivalent to the sodium content. Administration of such fluids is associated with a progressive elevation in serum chloride, resulting in hyperchloraemic acidosis.

The typical picture is of a persistent metabolic acidosis with a low/normal anion gap (< 18), high chloride and low bicarbonate. In most patients this is not physiologically significant, and will resolve as their condition improves. In those patients where the acidosis is severe (often multifactorial), or where there is a physiological or clinical effect (e.g. hyperkalaemia associated with acidosis occurring in a patient with renal dysfunction), reducing the chloride content of fluids and feeds and the use of sodium bicarbonate infusion will aid resolution. (See Metabolic acidosis, p. 212.)

The problems described above can be avoided by using balanced salt solutions, e.g. Hartmann’s or Ringer’s lactate solutions. Similarly, colloid solutions (both gelatins and starches), which were traditionally available suspended only in normal saline, are now available in balanced salt solutions. Although the evidence base in terms of outcomes is limited, it favours use of these over the traditional hyperchloraemic fluids. Follow local protocols or seek senior advice.

Energy requirements depend on body mass and metabolic rate. They are normally 30–40 kcal / kg / day, but this may be increased in critical illness. In most instances when starting nutritional support it is not necessary to calculate exact energy requirements. Standard feeds can be used and the energy content can be adjusted subsequently if necessary. If required, energy requirements can be estimated using formulae such as the one in Table 3.12, or measured with a metabolic computer attached to the breathing circuit (these measure O₂ uptake and CO₂ production to derive energy consumption). Longer term requirements should be assessed by a dietician.

TABLE 3.12 Estimated energy requirements (kcal / day)

An alternative method of estimating energy requirements is indirect calorimetry. Metabolic computers are available which sample the patient’s inspired and expired gases and, using an assumed value for the respiratory quotient, can estimate total energy expenditure.

Energy requirements are generally provided as a mixture of carbohydrate and fats.

To prevent muscle breakdown adequate amounts of nitrogen must be provided. This is generally of the order of 9–14 g nitrogen a day, equivalent to 1–2 g protein / kg per day. Proteins should be provided in a form that ensures that all the essential amino acids are provided. There is increasing interest in the role of individual amino acids. For example, glutamine has a specific role as a substrate for metabolism within the gastrointestinal tract where it is important in maintaining integrity and function. At the present time, there is no definitive evidence base for the benefit of such products.

Vitamins, minerals and trace elements are essential for health and many have important roles in enzyme pathways. Less is known, however, about the requirements during critical illness. Both water- and fat-soluble vitamins can be provided by commercially available preparations. Folic acid and vitamin B₁₂ should be prescribed separately. Trace elements and minerals, including calcium, magnesium, iron, zinc, copper, selenium, molybdenum, manganese and chromium, are available. Replacement is guided by the reference values for daily recommended intake and signs of deficiency. All patients with chronic alcohol dependency should receive vitamin B supplements (see p. 241).

There has been a lot of interest over the last 10 years in the role of several specific nutrients in modulating the immune response. Arginine, glutamine, nucleotides and omega-3 fatty acids have been studied, either alone or in combination, in a variety of patient groups. Studies have shown conflicting results, To date, there is no definitive evidence that immunonutrition improves outcome in critically ill patients.

Unless there is a specific surgical contraindication, all patients should receive enteral feeding as soon as possible, preferably within 24 h. This provides nutrition and helps to maintain gastrointestinal tract integrity and function. Potential benefits include:

Reduced gut atrophy.

Reduced bacterial and endotoxin translocation.

Reduced incidence of septic complications and SIRS.

Reduced length of hospital stay.

(See Stress ulcer prophylaxis, p. 172 and Gastrointestinal tract, p. 166.)

Contraindications include paralytic ileus, intestinal obstruction and surgical conditions of the oesophagus or abdomen.

The majority of patients in the ICU will already have a standard nasogastric tube in situ for gastric aspiration. This can be used for short-term feeding. In patients who require longer term feeding, fine-bore nasogastric feeding tubes are more comfortable and less likely to cause mucosal erosions. (See Practical procedures, p. 421.)

Delayed gastric emptying is a major factor limiting the success of enteral feeding. There is increasing use of feeding tubes placed through the pylorus, which deliver enteral feed directly into the duodenum or jejunum. Although it is possible to place these tubes ‘blindly’, more commonly placement is guided by X-ray screening, ultrasound or endoscopy. Percutaneous endoscopic gastrostomy (PEG) or gastrojejunostomy (PEGJ) is useful in patients who are likely to require long-term feeding. This can be performed on the ICU and has the advantage that it allows all nasogastric tubes to be removed, reducing the risks of nosocomial chest infections.

Enteral feeds are given by continuous infusion. Typically, feed is given for 20 h and then stopped for 4 h. This rest period is to allow the gastric pH to return to normal (acid) levels. This helps to prevent colonization of the stomach with gastrointestinal tract flora, which is associated with an increased incidence of nosocomial pneumonia. Many units have policies for the commencement of enteral feeding. For example:

Commence enteral feed at 30 mL / h.

Give feed for 4 h.

Aspirate NG tube to assess gastric residual volume.

If feed absorbed, increase in 25 mL increments every 4 h up to 100 mL / h.

The potential complications of enteral feeding are shown in Box 3.3.

Misplacement or dislodgement of the NG tube can result in accidental delivery and / or aspiration of feed into the lungs. The position of the tube must always be verified before feed or drugs are administered (see Passing a nasogastric tube, p. 421). Blocked NG tubes can occasionally be ‘rescued’ by flushing with normal saline using a syringe. Small syringes are more effective then large ones for this purpose.

High gastric residual volume suggests enteral feed is not being absorbed. If after 4 h feed the gastric residual volume is more than 200 mL, return the aspirated feed to the stomach and rest for 1 h. Then reassess.

If possible, stop or reduce opioid analgesics that may delay gastric emptying. Ensure that the electrolyte balance is normal. Disturbances of potassium and magnesium in particular can contribute to gastrointestinal tract dysfunction. Consider the need for further investigation such as plain abdominal X-ray to exclude obstruction. In the absence of mechanical obstruction the use of prokinetic drugs may promote gastric emptying. Choice will depend upon local protocol. Available agents include:

metoclopramide

erythromycin (lower dose for kinetic use).

Unless there is a contraindication to feeding, do not stop enteral feeds purely because of ‘failure to absorb’. Continue at a low rate, for example 10–20 mL / h. Consider the use of a nasoduodenal / nasojejunal tube.

Diarrhoea commonly complicates enteral feeding in the ICU. The causes of this are multifactorial. Diarrhoea is generally a nuisance rather than a serious problem; however, it may result in the need to abandon enteral feeding.

Do not immediately stop enteral feed. Discuss, with the dietician changing the feed, reduction in the osmolality and increase in the fibre content.

Perform a rectal examination to exclude faecal impaction (common in the elderly), which may be a cause of overflow diarrhoea. Consider suppositories or manual evacuation.

Confirm diarrhoea is not infective in nature: send stool specimens for microscopy and culture (Salmonella, Shigella and Campylobacter species) and for Clostridium difficile toxin.

Treat any infective process appropriately. For Clostridium difficile use oral or nasogastric metronidazole or vancomycin.

Review the drug chart. Stop any prokinetic drugs such as metoclopramide. If the diarrhoea is non-infective, consider the use of loperamide.

If the diarrhoea is bloody or if the nature is unclear, consider the need for further investigations e.g., sigmoidoscopy, colonoscopy or CT. Discuss with gastroenterology / infectious disease specialists.

Consider the need for a faecal tube collection system and isolation in a side room

Most units now use one or two standard mixture feeds, prepared under sterile conditions in the pharmacy or bought in from an outside supplier. The typical composition of a standard feed is shown in Table 3.13.

TABLE 3.13 Typical composition of standard TPN mixture

Some patients need regimens specifically tailored to their needs. For example, patients in renal failure, who are not on renal support, require a reduced volume and restricted nitrogen intake to avoid rises in plasma urea. For most patients, however, a standard feed can be started and advice subsequently sought from dieticians, pharmacists or a parenteral nutrition team. In practice therefore, decide what volume of feed the patient will tolerate. Standard adult feeds are usually 2.5 L a day, but smaller volume feeds are available for fluid-restricted patients.

Parenteral feeds are hypertonic and can cause thrombophlebitis. They should normally only be given via central venous lines, although high-volume lower-osmolality feeds may be given via peripherally inserted feeding lines. When inserting multiple lumen central lines, it is a good idea to keep one lumen clean and dedicated for TPN. Parenteral nutrition mixtures make good culture mediums for bacteria, so do not break the line to give anything else. TPN is given by constant infusion over 24 h and delivered by volumetric infusion pumps.

Advice should be sought from the nutrition team and dietician. The following should be assessed daily:

Fluid balance.

Urea, electrolytes, phosphate.

Glucose. Blood sugar will often rise and require the addition of an insulin infusion. Recent evidence suggests that close control of blood sugar levels may improve outcome of critically ill patients (see p. 215).

Adequate energy requirements. Judged by degree of catabolism clinically. Nitrogen balance can be calculated but in practice rarely is.

Liver function tests (albumin, transferrin and enzymes) indicate adequate protein synthesis and give an early indication of TPN-related complications.

Trace elements and micronutrient levels are typically measured weekly. Seek local advice.

The complications of TPN include all complications of central venous access (see Complications of central venous cannulation, p. 376). Metabolic derangement, particularly hyper- or hypoglycaemia, hypophosphataemia and hypercalcaemia, are common and require appropriate adjustment of the feed. Hepatobiliary dysfunction, including elevation of hepatic enzymes, jaundice and fatty infiltration of the liver, may occur. This is usually caused by a combination of the patient’s underlying disease processes and overfeeding. Reduce the volume of TPN and / or energy content. If the serum becomes very lipaemic, it may be necessary to reduce the fat content.

This syndrome was originally described in recovering prisoners of war, but is also well recognized in patients with anorexia nervosa who have been re-established on a healthy diet. It is seen but generally under recognized in critical illness. During starvation, there is suppression of insulin secretion, resulting in progressive loss of intracellular electrolytes. When effective feeding is re-established, there is a rapid rise in blood glucose, resulting in a shift from lipid to glucose metabolism. This is characterized by a rapid shift of electrolytes into cells, and in particular by profound hypophosphataemia. These changes are accompanied by a marked elevation in metabolic rate, and can be complicated by muscle weakness, rhabdomyolysis, cardiac failure, confusion and seizures. The syndrome can be managed by gentle reintroduction of nutrition, accompanied by meticulous monitoring and correction of fluid and electrolyte abnormalities (especially hypophosphataemia). Typically, at-risk patients are started on a quarter of their predicted daily requirements of nutrients and then this is gradually increased over a number of days. Seek specialist advice.